Recombinant granulocyte colony-stimulating factor (rG-CSF) increases circulating neutrophil number and function. We have shown that G-CSF pretreatment in a canine model of lethal bacterial peritonitis increases circulating neutrophil number, accelerates bacterial and endotoxin clearance, and improves cardiovascular function and survival. In a subsequent set of studies, we evaluated the effects of rG-CSF administered at the onset of bacterial sepsis rather than prophylactically. In these studies, we found that rG-CSF, despite administration at very high dosages (40 to 80 ug/kg q12h), did not result in increased circulating neutrophil numbers and did not appear to offer a protective advantage. These findings suggested that events associated with sepsis either directly inhibited the stimulatory effects of exogenous G-CSF or resulted in a maximal inflammatory response by the host that was insensitive to the effects of exogenous G-CSE In an additional set of studies to determine whether sepsis decreases the bone marrow response to G- CSF, we will evaluate bone marrow neutrophil precursor number in animals challenged with bacteria and treated therapeutically with G- CSF.